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Prevention of Bone Loss after Allogeneic Stem Cell Transplantation by Calcium, Vitamin D, and Sex Hormone Replacement with or without Pamidronate

Divisions of Endocrinology (K.K., M.J.V.) and Hematology (L.V., T.R.), Department of Medicine, and Departments of Obstetrics and Gynecology (K.L.) and Clinical Chemistry (H.A.), Helsinki University Central Hospital, FIN-00290 Helsinki, Finland

Address all correspondence and requests for reprints to: Dr. Matti Välimäki, M.D., Ph.D., Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland. E-mail: matti.valimaki{at}hus.fi.

Context: In controlled studies, bisphosphonates have been used to prevent bone loss after solid organ transplantations but not in conjunction with stem cell transplantation (SCT).

Objective: The objective of the study was to test whether additional iv pamidronate would prevent bone loss associated with SCT more effectively than the combination of calcium, vitamin D, and sex steroid replacement therapy alone.

Setting. The study was carried out at the Helsinki University Central Hospital.

Patients, Design, Intervention: Ninety-nine adult recipients of allogeneic SCT were randomized by age and gender into two groups. In one group, the patients received 1000 mg calcium carbonate and 800 IU vitamin D daily, and females received estrogen and males received testosterone replacement therapy. In another group, the patients received the same treatments plus six iv infusions of 60 mg pamidronate before and 1, 2, 3, 6, and 9 months after SCT.

Main Outcome Measures: Bone mineral density (BMD) of the lumbar spine and the upper femur, measured by dual-energy x-ray absorptiometry, and bone turnover markers were followed for 12 months.

Results: In the pamidronate group, lumbar spine BMD remained stable but decreased in the other group by 2.9% at 12 months (P = 0.0084 between the groups over time). Total hip BMD reduced 5.1% in the pamidronate group and 7.8% in the other group by 12 months (P = 0.0015), and femoral neck BMD reduced 4.2 and 6.2%, respectively (P = 0.074). In the pamidronate group, serum type I procollagen amino-terminal propeptide (P = 0.032 between the groups over time) and urinary type I collagen amino-terminal telopeptide (P = 0.035) decreased 79 and 68% during the first 3 months, and remained lowered thereafter, but did not change in the other group.

Conclusions: The recipients of allogeneic SCT receiving additional pamidronate sustain less bone loss than those treated with calcium, vitamin D, and sex steroid replacement alone. Despite all the efforts, however, bone loss is not totally abolished at the hip.

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